title: Constitutional CHEK2 mutations are infrequent in early-onset and familial breast/ovarian cancer patients from Pakistan.
abstract: BACKGROUND
  Less than 20% of Pakistani women with early-onset or familial breast/ovarian cancer harbor germ line mutations in the high-penetrance genes BRCA1, BRCA2 and TP53. Thus, mutations in other genes confer genetic susceptibility to breast cancer, of which CHEK2 is a plausible candidate. CHEK2 encodes a checkpoint kinase, involved in response to DNA damage.
  
  
  METHODS
  In the present study we assessed the prevalence of CHEK2 germ line mutations in 145 BRCA1/2-negative early-onset and familial breast/ovarian cancer patients from Pakistan (Group 1). Mutation analysis of the complete CHEK2 coding region was performed using denaturing high-performance liquid chromatography analysis, followed by DNA sequencing of variant fragments.
  
  
  RESULTS
  Two potentially deleterious missense mutations, c.275C>G (p.P92R) and c.1216C>T, (p.R406C), were identified (1.4%). The c.275C>G mutation is novel and has not been described in other populations. It was detected in a 30-year-old breast cancer patient with a family history of breast and multiple other cancers. The c.1216C>T mutation was found in a 34-year-old ovarian cancer patient from a family with two breast cancer cases. Both mutations were not detected in 229 recently recruited BRCA1/2-negative high risk patients (Group 2).
  
  
  CONCLUSIONS
  Our findings suggest that CHEK2 mutations may not contribute significantly to breast/ovarian cancer risk in Pakistani women.
authors.affiliation: Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Pakistan. u.hamann@dkfz-heidelberg.de
authors.forename: Muhammad U
authors.initials: MU
authors.lastname: Rashid
authors.forename: Noor
authors.initials: N
authors.lastname: Muhammad
authors.forename: Saima
authors.initials: S
authors.lastname: Faisal
authors.forename: Asim
authors.initials: A
authors.lastname: Amin
authors.forename: Ute
authors.initials: U
authors.lastname: Hamann
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000235:genetics*; D018567:Breast Neoplasms, Male / Q000235:genetics*; D064447:Checkpoint Kinase 2 / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D018095:Germ-Line Mutation; D006801:Humans; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D010051:Ovarian Neoplasms / Q000235:genetics*; D010154:Pakistan; D055815:Young Adult
chemical_list: D064447:Checkpoint Kinase 2